Microtubule stability, Golgi organization, and transport flux require dystonin‐a2/MAP1B interaction
Bibliographic record
Abstract
Loss of function of dystonin cytoskeletal linker proteins causes neurodegeneration in dystonia musculorum ( dt ) mutant mice. While much investigation has focused on understanding dt pathology, divergent functions of dystonin isoforms remain unclear. Here, we highlight novel functions of the dystonin‐a2 isoform in mediating microtubule (MT) stability, Golgi organization, and flux through the secretory pathway. Using dystonin mutant mice combined with isoform‐specific loss of function analysis, we find dystonin‐a2 is bound to MT associated protein 1B (MAP1B) in the centrosomal region, where it maintains MT acetylation. In dt neurons, absence of the MAP1B/dystonin‐a2 interaction results in altered MAP1B perikaryal localization, leading to MT deacetylation and instability. Deacetylated MTs result in Golgi fragmentation and prevent anterograde trafficking via motor proteins. Maintenance of MT acetylation through trichostatin A (TSA) administration or MAP1B overexpression in vitro , mitigates the observed defect. These aberrations are apparent in pre‐phenotype dorsal root ganglia (DRG) and primary sensory neurons, suggesting they are causal in the dt disorder.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".